OBJECTIVE: To evaluate the effects of
conventional treatment of chronic functional constipation on total and segmental
colonic transit times and on orocecal transit time.METHODS: A total of 34 consecutive patients with functional constipation
attending a specialized outpatient clinic were included in the study. Total
and segmental colonic transit times were assessed using radiopaque markers.
Hydrogen breath test was used to evaluate lactulose and bean orocecal transit
times. Treatment consisted of disimpaction, general and dietary fiber intake
instruction, and mineral oil administration.RESULTS: At admission, colonic dysmotility was found in 71.9% (23/32)
of patients. All patients who complied with the treatment showed improvement
of clinical symptoms after 6 weeks of treatment, when 82.6% (19/23) of those
with dysmotility at admission returned to normal or reduced the severity of
colonic transit patterns. Transit time decreased (medians) between admission
and eighth week of treatment: lactulose orocecal transit (from 70 to 50 minutes,
p = 0.002), bean orocecal transit (from 240 to 220 minutes, p = 0.002), and
total colonic transit (from 69.5 to 37.0 hours, p = 0.001). The need for mineral
oil therapy for constipation after a 12-month treatment was associated with
persistence of total colonic transit higher than 62 hours at the eighth week
of treatment (p = 0.014).CONCLUSION: The conventional therapeutic approach yielded good results
regardless of the presence or not of colonic dysmotility at inclusion in the
study. Digestive tract motility abnormalities in functionally constipated children
may be reversed, and may be secondary to constipation.

The conventional treatment of chronic functional
constipation involves, basically, the following procedures: fecal disimpaction
and maintenance to prevent reimpaction using a high-fiber diet, instruction in
the physiology of evacuation, and laxative therapy.1,2

In the etiology of chronic constipation, just
as all functional diseases of the digestive tract, there is an interaction of
biopsychosocial factors,3 with an emphasis on the vicious circle
of pain during defecation, leading to fecal retention, harder stools, and even
more painful defecation.1,3 It also involves constitutional factors,
a low-fiber diet, and motility disorders of the digestive tract characterized
by an increase in intestinal transit time, especially in the colon.1,4,5

An increase in total colonic transit time is
observed in about half of the patients with chronic constipation.1,4-6
Among various patterns of colonic dysmotility, outlet obstruction4,5
is traditionally considered the most frequent pattern; however, in our experience,
an expressive number of patients shows delayed transit time in the right colon,6,7
featuring colonic stasis. Little is known about the pathophysiological mechanisms
involved in the genesis of colonic motility disorders.1,8 Painful
defecation episodes, as a trigger for constipation, are likely to lead to stool
withholding maneuvers which result in lumpy and hard stools. This process, over
time, may cause rectal and sigmoid distension due to fecal continence.8

Hypothetically, distension of the colonic wall
may compromise its contraction and propulsive force, or even be accompanied
by the absence of high-amplitude peristaltic colonic waves, which propel stool
toward the rectum. This situation has been described in children with severe
refractory constipation, in whom colonic manometry did not reveal high-amplitude
peristaltic colonic waves, even after stimulation of a meal (gastrocolic reflex)
or administration of a peristaltic stimulant.9 Theoretically, fecaloma
emptying and maintenance treatment could also be accompanied by a reduction
in colon size with recovery of contraction force. These processes could affect
colonic transit time. Classic studies with healthy adult women showed that inflation
of rectal balloon or voluntary suppression of defecation lead to delayed gastric
emptying, which is called cologastric brake.10,11 In children, using
the hydrogen breath test after a bean test meal, we demonstrated delayed orocecal
transit time in chronic functional constipation with increased total colonic
transit time.6 Thus, rectal fecal impaction may cause disorders secondary
to colonic motility, gastric emptying, and small bowel transit. Only a few articles
have analyzed the evolution of the colonic transit time during conventional
treatment of chronic constipation, some of them focusing on the effect of dietary
fibers or prokinetic drugs on transit time.12-16

Therefore, the objective of the present study
is to analyze the effects of conventional treatment of chronic functional constipation
in patients attending a referral outpatient clinic on clinical symptoms, total
and segmental colonic transit times, and lactulose and bean test meal orocecal
transit times.

Patients and methods

Patients

The sample was composed of 34 patients with clinical
diagnosis of chronic functional constipation, consecutively admitted to the
Constipation Clinic of the Discipline of Pediatric Gastroenterology, Universidade
Federal de São Paulo  Escola Paulista de Medicina (UNIFESP-EPM),
São Paulo, southeastern Brazil. Patients unable to perform voluntary
collection of air samples for the hydrogen breath test , using antibiotics in
the 4 weeks prior to examination, with constipation secondary to Hirschsprung's
disease, spinal or anal anomalies, metabolic diseases, and cerebral palsy were
excluded from the study.

Chronic constipation was characterized by hard
stools that were painful or difficult to pass, associated or not with longer
intervals between evacuations, blood mixed with stools, fecal retention, and
soiling for over a 3-month period.1,6,7,13 When necessary, anorectal
manometry was performed, as well as additional examinations, to rule out other
non-functional causes of chronic constipation as recommended.1,2,17

Study design

In this prospective cases series of patients
with chronic functional constipation, we assessed lactulose and bean test meal
orocecal intestinal transit times (5-day interval between each test), oroanal
transit time of carmine dye, and total and segmental colonic transit times with
radiopaque markers. These measurements were conducted at admission (before treatment
started) and at the sixth week of treatment.

At month 12, after mineral oil was discontinued
for at least 15 days, we reassessed bean test meal orocecal transit time and
oroanal transit time of carmine dye.

Methods

Clinical information and data collection

An individual standardized form including the
following clinical parameters was used: defecation frequency, pain during defecation,
fear or effort during defecation, fecal retention, stool consistency and shape,
presence of soiling, blood mixed with stools, and abdominal distension and pain.
A complete physical examination, including a rectal examination, was also performed.

Follow-up appointments were conducted every 2
weeks to collect relevant clinical information. In addition, a physical examination
focusing on fecal impaction was performed. All assessments were carried out
by the same investigator (A.C.F.S.).

Therapy regimen

At inclusion in the study, when necessary, disimpaction
was performed with phosphate enema for 2 to 5 days. Patients were then prescribed
a high-fiber diet and mineral oil at a dose of 1-3 mL/kg/day, in two divided
doses. General instruction in the physiology of evacuation and bowel training
including defecation in the toilet after meals were also part of the therapy
regimen. At follow-up appointments, when necessary, mineral oil dose was adjusted.
In the case of reimpaction, disimpaction procedures were repeated.1,18

Hydrogen breath test to assess orocecal transit time

The hydrogen breath test was used to assess orocecal
transit time after ingestion of lactulose and a test meal of cooked beans.

Tests were performed after a 12-hour fast. Before
examinations, oral cleaning was performed with 0.05% chlorhexidine. Stools were
collected and breath hydrogen concentration was determined, respectively, using
the GaSample system and a model 12i Quintron Microlyser gas chromatograph, both
purchased from Quintron Instrument Co. Inc. (Menomonee Falls, Wisconsin, USA).6,7

Orocecal transit time was defined as the time
between the ingestion of lactulose or beans and a rise of 10 ppm in baseline
breath hydrogen concentration, in each of two consecutive samples.5

To assess lactulose orocecal transit time, after
collecting baseline fasting samples of end-expired air, a 10-g 10% dilute lactulose
solution was administered orally. After the ingestion of lactulose, serial 10-minute
samples of end-expired air were collected for 180 minutes (end of the test).
Cases in which a minimum 10-ppm rise was not achieved in the fasting breath
hydrogen concentration, the test was extended to 240 minutes.6

The child was defined as not producing hydrogen
when peak hydrogen in exhaled air was lower than 10 ppm in relation to baseline
in samples collected until 240 minutes in the lactulose breath test.5

Total and segmental colonic transit times

Total and segmental colonic transit times were assessed using radiopaque markers,
according to the technique described by Metcalf et al.19 For this
examination, three capsules with 24 radiopaque markers of three distinctive
types were used, as described previously in sufficient detail.6,7
Each child ingested one capsule with 24 markers on three consecutive mornings.
On the fourth day, a plain anteroposterior abdominal radiograph was performed.
An additional radiograph was performed at day 7 if more than 80% of the markers
remained in the previous film. Radiographs were performed using high-sensitivity
and high-kilovoltage films, allowing a reduction in radiation dose of approximately
1/4 in relation to conventional radiographs.

Total and segmental colonic transit times were
calculated according to a previously described formula.19 The patterns
of colonic motility disorder were defined according to the following criteria20-22:

- Outlet obstruction: delayed rectosigmoid
transit time;
- Distal obstruction: delayed left colonic transit time associated or not
with delayed rectosigmoid transit time;- Right colonic stasis: delayed right
colonic transit time associated or not with delayed left colonic and rectosigmoid
transit times;- Normal colonic transit: normal colonic
transit in the three segments.

The upper limits of the normal range for right
colon, left colon, and rectosigmoid total colonic transit time were, respectively,
62, 18, 20, and 34 hours.19

Oroanal transit time of carmine

Children were given 500 mg oral carmine diluted
in 50 mL water. Mothers were instructed to write down the date and time when
the stools changed color. Oroanal transit time was defined as the time between
the ingestion of carmine dye and its initial appearance with stools.23

Statistical analysis

Statistical calculations were conducted using
the Jandel Sigma Stat software. In all cases, the level of rejection for null
hypothesis was set at a p value less than or equal to 0.05 (5.0%). The several
tests used are specified along with the results. Median and 25th and 75th percentiles
(shown in parentheses) were used to express those variables with non-normal
distribution. The other variables were expressed as mean and standard deviation.

The project was analyzed and approved by the Research Ethics Committee of UNIFESP-EPM.
Written and signed informed consent was obtained from children's guardians and
from those children aged over 12 years.

Results

A total of 34 patients with median age (25th and 75th percentiles) of 93.7
(74.3-107.4) months were included in the study, minimum age of 3 and maximum
of 13 years. Regarding sex, 19 were boys and 15 were girls. Median age at onset
of constipation was 12 (4 and 48) months. In 15 (44.1%) of 34 patients, first
symptoms occurred during the first year of life, in six (40.0%) of these 15
patients occurring during the first 6 months of life. Soiling was found
in 29 (85.3%) of 34 patients. Median age at onset of soiling was 60 (48 and
68) months. Soiling starting before 48 months of age occurred in nine (31.0%)
of 29 patients. These nine patients had already learned sphincter control before
the onset of soiling. Median soiling frequency was 7 (3 and 7) days per week,
i.e., most patients presented daily soiling. Of the 34 patients admitted, only
one did not attend follow-up clinical and transit time reassessment at the eighth
week of treatment, since the family moved to another city.

Table 1 shows clinical characteristics of 33 patients
reassessed at the sixth week of treatment. At the sixth week of treatment, 30
(90.9%) of 33 patients were asymptomatic. Of the remaining three symptomatic
patients, one patient showed persistence of soiling, pain and effort during
defecation; one patient showed pain during defecation; and another patient showed
fear of defecation. Statistical analysis revealed statistically significant
reduction in all clinical manifestations of constipation in relation to baseline
assessment. A statistically significant increase was observed in the number
of weekly defecations.

Table 2 shows orocecal transit times after lactulose
administration and after a bean test meal at admission and at the sixth week
of treatment. Statistical analysis revealed statistically significant reduction
in both lactulose and bean orocecal transit times. A statistically significant
reduction was also observed in oroanal transit time and total and segmental
colonic transit times. It is worth mentioning that all patients analyzed both
at admission and at the sixth week of treatment and after a 1-year treatment
were hydrogen producers.

Taking into account the 64 measurements of oroanal carmine and total colonic
transit times with radiopaque markers, Sperman's correlation coefficient was
calculated, being equal to +0.87 (p < 0.001).

Two of 34 patients included in the study were not reassessed for total and segmental
colonic transit times at the sixth week (one moved to another city, and the
other did not undergo these examinations but continued with treatment and follow-up).
Regarding the pattern of colonic motility disorder at the sixth week of treatment,
22 (68.7%) of 32 patients showed normal transit time in the three segments.
In the remaining patients: three (9.4%) showed right colonic stasis, three (9.4%)
showed distal obstruction, and four (12.5%) showed outlet obstruction, as described
in Table 3.

When possible, patients with chronic functional constipation were reassessed
6 and 12 months after admission to the study.

At month 6, a clinical reassessment was performed in 33 of the 34 initial
study patients. Of these 33 patients, 28 (84.8%) were asymptomatic. Five (15.2%),
despite regular use of mineral oil, needed one or two rectal enemas for fecal
disimpaction after maintenance treatment had started. At this assessment, only
six (18.1%) patients did not need mineral oil to maintain a positive bowel habit.

At month 12, 24 (72.7%) of 33 patients remained on follow-up. Of these 24
patients, 22 (91.6%) were asymptomatic. Two (8.3%) needed intestinal lavage
when mineral oil was discontinued. After reintroduction of the laxative, positive
bowel habit was reinstated. Of the 24 patients, 12 (50.0%) continued on mineral
oil. Of these 12 patients, 10 (83.3%) had shown total colonic transit time higher
than 62 hours before treatment started, whereas six (50.0%) of the 12 who did
not need mineral oil showed total colonic transit time higher than 62 hours
(p = 0.193, two-tailed Fisher's exact test). At the sixth week of treatment,
the 12 (100%) who did not need mineral oil at month 12 showed total colonic
transit time lower than 62 hours, whereas, of the 12 who still needed mineral
oil at month 12, only six showed normal total colonic transit time lower than
62 hours at the sixth week of treatment (p = 0.014, two-tailed Fisher's exact
test).

Of the 24 patients, 17 (70.8%) agreed to repeat, at month 12, orocecal transit
time with bean test meal and oroanal transit time (carmine). Table
4 shows orocecal and oroanal transit times of these 17 patients at admission,
at the sixth week of treatment and after a 12-month follow-up period. It is
important to point out that, prior to the assessments at 12 months, administration
of laxative was discontinued in all patients for at least 15 days.

Discussion

At the sixth week of treatment, including mineral
oil administration, we observed a statistically significant reduction in lactulose
and bean test meal orocecal transit times, in oroanal transit time of carmine,
and in total colonic transit time measured with radiopaque markers (Table
2). We also observed changes in the patterns of colonic dysmotility toward
normal patterns or exclusive involvement of distal colonic portions (Table
3). At this time point, almost all patients showed positive clinical response,
indicating that dysmotility patterns at admission are not predictive of outcome
at the initial phase of treatment, even for those patients who showed right colon
stasis. Decreased transit is likely to have resulted from cessation of fecal retention
and fecaloma emptying, neutralizing the phrenocolonic reductive effect on the
proximal motility of the digestive tube.8,11,12 Only one study analyzed
orocecal transit time during treatment and did not show its reduction,24
in opposition to our data, which showed a decrease in this parameter using both
lactulose and bean test meal. It is worth mentioning that dysmotility of the proximal
digestive tube may be associated with symptoms in the upper abdomen, such as early
saciety, which may disappear after fecaloma emptying.6,8,10,12

Regarding total and segmental colonic transit
times, it is difficult to compare our results with the few studies found in
the literature, considering that distinct therapy regimens14,16,24,25
or patients with constipation associated with neurological involvement were
analyzed.15 Regarding our patients with clinical symptoms improved
upon prescription of therapy regimen, one can speculate that a reduction in
colonic dimensions may have occurred, which could have contributed to returning
to a normal peristaltic function. This hypothesis cannot be confirmed in practice
due to ethical restrictions inherent to colon-contrasted serial radiographs
to demonstrate reduction in its dimensions. Within this context, in the group
of 17 patients who agreed to repeat the measurement of carmine oroanal transit
time after one year of treatment, mineral oil discontinued for at least 2 weeks,
median time remained at 30 hours as observed since the sixth week of treatment,
pointing out a high correlation (r = +0.89) between total and oroanal colonic
transit time of carmine. These results could be interpreted as suggesting, in
children, that colonic motility abnormalities of functional constipation might
be reversed, even after cessation of laxatives, that is, they are secondary
to constipation.

Our data also show a higher probability of laxative
need after 1 year of treatment in patients with persistence of delayed total
colonic transit time at the sixth week of treatment, underscoring the importance
of the initial phase of treatment. In Dutch children with functional constipation
treated with a therapy regimen similar to that used in the present study, the
authors observed that a negative evolution after 1 year of treatment was associated
with a total colonic transit time higher than 100 hours.12 In our
study, we observed that, at admission, nine (28.4%) of the 34 patients showed
total colonic transit time higher than 100 hours (data not shown). After a 12-month
follow-up period, six of these nine patients remained on mineral oil, confirming
that a total colonic transit time higher than 100 hours at baseline assessment
may be an indicator of a worse prognosis. We should highlight that, due to the
small number of patients, no statistically significant association was obtained.
Thus, in our opinion, the main limiting factor of our study lies in the lack
of possibility to repeat baseline assessments after a 1-year follow-up, which
is common in clinical studies in which some patients are expected to withdraw
treatment protocol, especially those fully recovered. Another aspect refers
to patient severity, that is, the results from the present study cannot be extrapolated
to all functionally constipated children, especially to those with less severe
functional constipation who do not attend specialized clinics.

Of the patients followed for up to 1 year after
treatment, half of them still needed mineral oil to maintain an adequate bowel
habit, which is consistent with the scarce information found in the literature
concerning improvement of clinical symptoms of constipated patients followed
for at least 1 year in specialized clinics.12,26-28

In conclusion, the conventional therapeutic approach
yielded good results regardless of the presence or not of colonic dysmotility
at inclusion in the study. The persistence of delayed total colonic transit
time at the sixth week of treatment indicates a higher probability of laxative
need after 1 year of treatment. Digestive tract motility abnormalities in functionally
constipated children may be reversed, and may be secondary to constipation.

2. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Evaluation and treatment of constipation in children: summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2006;43:405-7. [ Links ]